Demethoxycurcumin was prior to temozolomide on inhibiting proliferation and induced apoptosis of glioblastoma stem cells

Abstract

Temozolomide (TMZ) is widely used for treating glioblastoma (GBM), which can effectively inhibit the GBM growth for some months; however, it still could not prevent the invariable recurrence of GBM. The existence of glioma stem cells (GSCs) was considered to be a key factor. But TMZ has poor effects on GSCs. Recently, demethoxycurcumin (DMC) has been shown to display anti-tumor activities in malignant gliomas. However, its effects and the potential mechanisms on GSCs were still unclear. Our study showed that DMC was prior to TMZ on resulting in a significant increase in GSC apoptosis and a marked inhibition of cell growth in vitro. And combined treatment of DMC and TMZ showed more significant anti-GSC effects. Further research into the underlying mechanism demonstrated that this novel combinatorial regimen leads to changes of multiple cell signaling pathways including reactive oxygen species (ROS) production and caspase-3 signaling mitochondria-related apoptosis activation as well as inactivation of JAK/STAT3 signaling pathway. Taken together, our data demonstrate that the anti-GSC effects of DMC are better than TMZ, and combined treatment of DMC and TMZ has much stronger effects on GSCs.

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Acknowledgments

This work was supported by the China Natural Science Foundation (81000963 and 81370062), Jiangsu Province’s 333 Talent Program (BRA2011046), Jiangsu Province “six personnel peak” funded projects (2013-WSN-145/028), Jiangsu Province’s Natural Science Foundation (BK2012670), Medical Research Foundation by Jiangsu Province Health Department (YG201301 and Z201318), the Clinical Technology Development of Jiangsu University (JLY20120053), the Kunshan Social Development Foundation (KS1006, KS1009), and the Suzhou Social Development Foundation (SYS201063). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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All authors have declared the sources of research funding for this manuscript and have no financial or other contractual agreements that might cause (or be perceived as causes of) conflicts of interest.

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Correspondence to Lei Shi or Zhimin Wang.

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Lei Shi and Xifeng Fei contributed equally to this work.

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Shi, L., Fei, X. & Wang, Z. Demethoxycurcumin was prior to temozolomide on inhibiting proliferation and induced apoptosis of glioblastoma stem cells. Tumor Biol. 36, 7107–7119 (2015). https://doi.org/10.1007/s13277-015-3427-x

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Keywords

  • Temozolomide
  • Demethoxycurcumin
  • Glioblastoma stem cell
  • Proliferation
  • Apoptosis